The present invention relates to the diagnosis of septic complications. The term “sepsis” has been used to describe a variety of clinical conditions related to systemic manifestations of inflammation accompanied by an infection. Because of clinical similarities to inflammatory responses secondary to non-infectious aetiologies, identifying sepsis has been a particularly challenging diagnostic problem. In this respect, definitions have been provided for “Systemic Inflammatory Response Syndrome” (or “SIRS”), which refers generally to a severe systemic response to an infectious or non-infectious insult, and for the related syndromes “sepsis,” “severe sepsis,” and “septic shock” (Bone et al., Chest 101:1644-53, 1992). SIRS may be related to both infection and to numerous non-infective aetiologies, including trauma.
Despite the availability of antibiotics and supportive therapy, sepsis represents a significant cause of morbidity and mortality. Several laboratory tests have been investigated for use, in conjunction with a complete clinical examination of a subject, for the diagnosis/prognosis of sepsis (Giamarellos-Bourboulis et al., Intensive Care Med. 28: 1351-56, 2002).
Several molecular markers have been discussed to facilitate diagnosis and treatment monitoring of sepsis in humans and several animal species. The most widely used ones may be CRP (C-reactive protein) and PCT (procalcitonin).
Also various interleukins have been discussed as potential biomarkers of sepsis. However they are of limited use at present because of a lack of specificity. For example, Carrigan et al. (Clinical Chemistry 50 (8) (2004) 1301-1314) reported the following sensitivities and specificities for these markers in humans:
TABLE 1ROC analysis results for various biomarker-basedprediction of sepsis in adult and neonatal cases.aROC analysisReferencedMarkerAge groupCutoff rangeSensitivity, %Specificity, %studiesTNFαAdults11.5ng/L5566(38)Neonates12-20ng/L67/79/8843/71/86(23, 61 63)IL-6Adults50-200ng/L51/67/8653/65/79(30, 35, 36, 66)Neonates10-160ng/L 71/84/10043/71/96(26, 29, 61, 63,70-72)IL-1raChildrenNAb3389(85)Neonates10.9μg/L9392(70)IL-8Adults30-340ng/L57/63/6857/76/93(30, 35, 85)Neonates50ng/L9270(61)CRPAdults4-150mg/L35/69/8918/61/81(30, 35, 36, 38,46 66, 88, 89)Neonates1-23mg/L43/65/96 80/90/100(22, 26, 63, 70,89, 90)PCTAdults0.4-81μg/L65/81/9748/73/94(30, 35-38, 43,46, 66, 88, 89,122, 123)Neonates1.0-61μg/L77/85/9962/83/91(22, 72, 89, 90)aValues listed are for differentiating infected individuals from uninfected controls rather than from healthy individuals.Sensitivities and specificities Ested are minimum, mean [in bold], and maximum percentages.bNA. not avalable.
This overview may be found in EP 2 060 920 A1.
These data show that even in humans, where septic disease patterns are extensively investigated, sensitivity and specificity of current markers can (even as mean values) come down to as low as 33% and 66% respectively, not to mention the in homogeneity of presently published data.
These data show that there is definitely a need for new diagnostic markers with improved diagnostic characteristics. Therefore, the diagnosis of sepsis, especially early diagnosis of sepsis, is still a great need in clinical medicine. An optimum diagnosis should reveal persons with a risk of developing sepsis or persons being at an early stage of sepsis. Specifically in systemic inflammation, i.e. in multiply traumatized patients such a diagnosis is often very difficult because of other pathological processes interfering with the “normal” physiological values and parameters measured in standard intensive care medicine.
Diagnosis of sepsis in patients with systemic inflammation, e.g. complications in polytraumatised patients is a very specific problem for which a high need exists in intensive care medicine.
It is therefore an object of the present invention to provide a suitable method for diagnosing sepsis, being sensitive and/or specific.